Human peripheral blood monocytes mediated ADCC (antibody-dependent cellular cytotoxicity) against sheep RBC primarily through surface FcRI (Fc receptor I). A decrease in the ADCC ability was noticed when monocytes were cultured overnight at 37 degrees C. The decrease was accompanied with a down-regulation in the expression of surface fcRI on cultured monocytes, since agents (cytochalasin-D and monensin) which maintained the expression of FcRI were able to prevent the fall in the cytotoxic ability of cultured monocytes. Monocytes did not require de novo protein synthesis for their lytic activity against sensitized SRBC (Sheep red Blood cells) . There was an augmentation of monocyte-mediated ADCC in the presence of protein synthesis inhibitors, suggesting possible existence of an endogenous inhibitor.